Ion trap mass analyzers are widely used for MS/MS or MSn analysis, in which one or more stages of isolation and fragmentation of precursor ions is performed to generate and analyze product ions. Precursor ions are typically fragmented in an ion trap by the collision induced dissociation (CID) method, whereby the ions are kinetically excited by the application of a excitation voltage to electrodes of the ion trap, such that the excited ions undergo energetic collisions with atoms or molecules of damping gas (also referred to as collision or buffer gas). The CID method is described in U.S. Pat. No. Re 34,000 to Syka et al.
It has long been known that in order to obtain optimal fragmentation efficiency using CID, it is necessary to tune the collision energy for the precursor ion of interest. Schwartz et al. (U.S. Pat. No. 6,124,591) observed a generally linear relationship between the mass-to-charge ratio (m/z) of the precursor ion and its optimal collision energy, and prescribed varying the amplitude of the applied excitation voltage in accordance with this relationship. In an alternative approach, Yoshinari et al. (U.S. Pat. No. 6,683,303) teaches adjusting the duration of application of the excitation voltage based on the m/z of the precursor ion. While these techniques are employed with some success in commercial instruments, the optimal collision energy also depends on molecular properties other than m/z as well as instrument operating parameters, and so predicted values of excitation voltage amplitude or duration based solely on precursor ion m/z may not uniformly yield high abundances of fragment ions for different ion species or across a range of operating conditions.
Mulholland et al. (“Multi-Level CID: A Novel Approach for Improving MS/MS on the Quadrupole Ion Trap”, Proc. 47th Ann. Conf. on Mass Spectrometry, 1999) describes one approach for avoiding the problems associated with collision energy optimization. This approach involves applying the excitation voltage in a stepped fashion, whereby the excitation voltage amplitude is successively increased from a minimum value to a maximum value in discrete increments. The minimum, maximum, and intermediate excitation voltage amplitudes (a total of five amplitude levels are employed in a representative implementation) may be automatically calculated based on the m/z of the precursor ion, the calibrated resonance ejection voltage for the precursor ion, and the pseudo-potential well model. By using successively increasing collision energies, the possibility of ejecting precursor ions before fragmentation is diminished, and the odds of obtaining favorable ion fragmentation efficiencies are increased.
Specht et al. (U.S. Pat. No. 7,232,993) discloses a CID technique that attempts to optimize fragmentation energies by taking into account both the m/z of the precursor ion and the Mathieu parameter q, which is directly proportional to the amplitude of the trapping voltage and inversely proportional to the precursor ion m/z. In one implementation of this technique, a fragmentation-optimized excitation voltage amplitude is selected based on the values of precursor ion m/z and q; and fragmentation is carried out at the selected amplitude; according to another implementation, fragmentation-optimized values of the excitation voltage amplitude and q are determined based on the precursor ion m/z, and fragmentation is carried out at these values by appropriately adjusting the trapping voltage amplitude in addition to the excitation voltage amplitude.
There remains a need in the art for a CID technique that will yield high fragmentation efficiencies for a variety of ion types and over a range of operating conditions.